The protection of carbonyl compounds, in particular aldehydes, by acetalization is a common and useful technique for multi-step synthesis in drug design, organic and carbohydrate chemistry, and in the pharmaceutical industry. Acetals are also commonly used in detergents, cosmetics and fragrances. Acetalization serves to protect the carbonyl group from the attacks of several reagents such as nucleophiles, oxidants, hydrides and organo-metallic reagents.
A typical method of acetalization involves a reaction with alcohol or diol using an inorganic acid such as hydrochloric acid as the catalyst. In this reaction, water is usually removed from the reaction to shift the equilibrium towards the right to increase product yield. The removal of water may be achieved by physical processes such as azeotropic distillation, or through chemical means such as the addition of drying agents to the reaction e.g., trialkylorthoformate. However, the use of corrosive hydrochloric acid (HCl) remains a disadvantage.
Many other types of catalysts have also been reported to catalyze the acetal protection of carbonyls. These catalysts include conventional acids such as trifluoroacetic acid (TFA), p-Toluenesulfonic acid (p-TSA), Lewis acids; functionalized silica; metal chlorides; metal triflates; transition metal complexes; natural materials such as kaolinitic clay; and organic compounds such as N-bromosuccinimide (NBS), 2,6-pyridinedicarboxylic acid (PDA), trichloromethylsilane and tetrabutylammonium tribromide (TBATB). Acetalization carried out under basic conditions, involving the use of NH3 and Et3N with TiCl4 catalyst are also known.
However, the above-mentioned conventional means and list of catalysts do not overcome the disadvantages and limitations which comprises the use of corrosive acid catalyst, high reaction temperatures (such as greater than 60° C. to 150° C.), expensive reagents, poor chemo-selectivity, incompatibility for substrates containing acid-sensitive functional groups, and difficulty in catalyst recovery and recycling without loss in catalytic activities.
Accordingly, there is a need for a catalyst that ameliorates the above limitations.
There is a need to provide a method of acetalizing an aldehyde that overcomes, or at least ameliorates, one or more of the disadvantages described above.